Chapter 30: Disorders of Heptaobiliary and Exocrine Pancreas Function Porth

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Chapter 30: Disorders of Heptaobiliary and Exocrine Pancreas Function Porth - Essentials of Pathophysiology - 3rd edition

The liver, the gallbladder, and the exocrine pancreas are classified as _____ organs of the gastrointestinal tract.

accessory

Approximately 300 mL of blood per minute enters the liver through the hepatic _____; another 1050 mL/minute enters by way of the ____.

artery, portal vein

The venous blood delivered by the ____ comes from the digestive tract and major abdominal organs, including the pancreas and spleen.

hepatic portal vein

A major exocrine function of the liver is _____ secretion.

bile

The most important of the secretory proteins of the liver is _____.

albumin

Acetyl-CoA units from fat metabolism also are used to synthesize ____ and _____ acids in the liver.

cholesterol, bile

Almost all the _____ synthesis in the body from carbohydrates and proteins occurs in the liver.

fat

Whenever a greater quantity of carbohydrates enters the body that can be immediately used, the excess is converted to _____ in the liver.

triglycerides

Bile salts serve as an important function in digestion; they aid in ____ dietary fats, and they are necessary for the formation of the _____ that transport fatty acids and fat-soluble vitamins to the surface of the intestinal mucosa for absorption.

emulsifying, micelles

____ represents a decrease in bile flow through the intraheptatic canaliculi and a reduction in secretion of water, bilirubin, and bile acids by the heptaocytes.

Cholestasis

Common to all types of obstructive and hepatocellular cholestasis is the accumulation of _____ pigment in the liver.

bile

_____ jaundice occurs when red blood cells are destroyed at a rate in excess of the liver's ability to remove the bilirubin from the blood.

Hemolytic

_____ of bilirubin is impaired whenever liver cells are damaged, when transport of bilirubin into liver cells becomes deficient, or when the enzymes needed to conjugate the bile are lacking.

Conjugation

_____ result in chemical modification of reactive drug groups by oxidation, reduction, hydroxylation, or other chemical reactions carried out in hepatocytes.

Phase 1 reactions

Drugs such as alcohol and barbiturates can induce certain members of the _____ family to increase enzyme production, accelerating drug metabolism and decreasing the pharmacologic action of the drug.

CYP or cytochrome P450 gene

______, which involve the conversion of lipid-soluble derivatives to water-soluble substances, may follow phase I reactions or proceed independently.

Phase 2 reactions

Direct hepatotoxic reactions result from drug metabolism and the generation of _____.

toxic metabolites

_____ drug reactions result in decreased secretion of bile or obstruction of the biliary tree.

Cholestatic

_____ refers to inflammation of the liver.

Hepatitis

Currently, recreational _____ use is the most common mode of hepatitis C virus transmission in the United States and Canada. The main route of transmission of hepatitis C virus in the past was through contaminated _____ or blood products and ______.

injection drug, blood transfusions, high-risk sexual behavior

_______ hepatitis is a severe type of chronic hepatitis of unknown origin that is associated with high levels of serum immunoglobulins, including autoantibodies.

Autoimmune

_____ biliary diseases disrupt the flow of bile through the liver, causing cholestasis and biliary cirrhosis.

Intrahepatic

_____ biliary cirrhosis results from prolonged obstruction of the extrabiliary tree.

Secondary

Obesity, type 2 diabetes, the metabolic syndrome, and hyperlipidemia are coexisting conditions frequently associated with _____ liver disease.

fatty

____ represents the end stage of chronic liver disease in which much of the functional liver tissue has been replaced by fibrous tissue.

Cirrhosis

_____ is characterized by increased resistance to flow in the portal venous system and sustained portal vein pressure above 12 mmHg.

Portal hypertension

Complications of portal hypertension arise from the _____ pressure and _____ of the venous channels behind the obstruction.

increase, dilation

_____ occurs when the amount of fluid in the peritoneal cavity is increased.

Ascites

_____ is a complication in persons with both cirrhosis and ascites.

Spontaneous bacterial peritonitis

The _____ syndrome refers to a functional renal failure sometimes seen during the terminal stages of liver failure with ascites.

hepatorenal

Hepatic _____ refers to the totality of central nervous system manifestations of liver failure.

encephalopathy

Among the factors identified as etiologic agents in _____ are chronic viral hepatitis, cirrhosis, long-term exposure to environmental agents such as aflatoxin, and drinking water contaminated with arsenic.

liver cancer

The _____ is a distensible, pear-shaped, muscular sac located on the ventral surface of the liver.

gallbladder

_____ provides a strong stimulus for gallbladder contraction and is released when food enters the intestines.

Cholecystokinin

Gallstones are caused by precipitation of substances contained in bile, mainly _____ and _____.

cholesterol, bilirubin

Acute _____ is a diffuse inflammation of the gallbladder, usually secondary to obstruction of the gallbladder outlet.

cholecystitis

The ______ pancreas is made up of lobules that consist of acinar cells, which secrete digestive enzymes into a system of microscopic ducts.

exocrine

Acute _____ represents a reversible inflammatory process of the pancreatic acini brought about by premature activation of pancreatic enzymes.

pancreatitis

_____ is characterized by progressive destruction of the exocrine pancreas, fibrosis, and in the later stages, by destruction of the endocrine pancreas.

Chronic pancreatitis

The most significant and reproducible environmental risk factor of pancreatic cancer is ______.

cigarette smoking

Define Kupffer cells

Capable of removing and phagocytosing old and defective blood cells.

Define Albumin

Transport protein/plasma colloidal osmotic pressure

Define Gluconeogenesis

Amino acids are used for producing glucose

Define oxidation deamination

Conversion of amino acids to ketoacids and ammonia

Define beta oxidation

The splitting of fatty acids into two-carbon acetyl-coenzyme A.

Define Extrahepatic cholestasis

Obstruction of the large bile ducts that reduces bile secretion

Define bilirubin

Formed from senescent red blood cells

Define jaundice

Abnormally high accumulation of bilirubin in the blood

Define steatosis

Fatty infiltration of the liver

Define cholestatic jaundice

Occurs when bile flow is obstructed between the liver and the intestine.

Define Hepatitis A

Occurs primarily by the fecal-oral route

Define Hepatitis B

Inoculation with infected blood and/or spread by oral or sexual contact

Define Hepatitis C

The most common cause of chronic hepatitis, cirrhosis, and hepatocellular cancer in the world.

Define Hepatitis D

Infection is linked to hepatitis B

Define Hepatitis E

Does not cause chronic hepatitis or the carrier state

What are the basic functions of the liver?

The liver is one of the most versatile and active organs in the body. It produces bile; metabolizes hormones and drugs; synthesizes proteins, glucose, and clotting factors; stores vitamins and minerals; changes ammonia produced by deamination of amino acids to urea; and converts fatty acids to ketones. The liver degrades excess nutrients and converts them into substances essential to the body. In its capacity for metabolizing drugs and hormones, the liver serves as an excretory organ.

Describe the pathogenesis of cholestasis.

A number of mechanisms are implicated in the pathogenesis of cholestasis. Primary biliary cirrhosis and primary sclerosing cholangitis are caused by disorders of the small intrahepatic canaliculi and bile ducts. In the case of extrahepatic obstruction, such as that caused by conditions such as cholelithiasis, common duct strictures, or obstructing neoplasms, the effects begin with increased pressure in the large bile ducts. Genetic disorders involving the transport of bile into the canaliculi also can result in cholestasis.

List the major causes and categories of jaundice.

The four major causes of jaundice are excessive destruction of red blood cells, impaired uptake of bilirubin by the liver cells, decreased conjugation of bilirubin, and the obstruction of bile flow in the canaliculi of the hepatic lobules or in the intrahepatic or extrahepatic bile ducts. From an anatomic standpoint, jaundice can be categorized as prehepatic, intrahepatic, and posthepatic.

What is measured in the serum to assess liver dysfunction?

Elevated serum enzyme tests usually indicate liver injury earlier than other indicators of liver function. The key enzymes are alanine aminotransferase (ALT) and aspartate aminotransferase (AST), which are present in liver cells. Alanine aminotransferase is liver specific, whereas aspartate aminotransferase is derived from organs other than the liver. In most cases of liver damage, there are parallel rises in alanine aminotransferase and aspartate aminotransferase. The most dramatic rise is seen in cases of acute hepatocellular injury.

Describe the clinical course of viral hepatitis.

The clinical course of viral hepatitis involves a number of syndromes, including asymptomatic infection with only serologic evidence of disease, acute hepatitis, the carrier state without clinically apparent disease or with chronic hepatitis, chronic hepatitis with or without progression to cirrhosis, with rapid onset of liver failure. Not all hepatotoxic viruses provoke each of the clinical syndromes.

How does ethanol cause tissue damage?

The metabolic end products of alcohol metabolism (e.g. acetaldehyde, free radicals) are responsible for a variety of metabolic alterations that can cause liver injury. Acetaldehyde, for example, has multiple toxic effects on liver cells and liver function. The metabolism of alcohol leads to chemical attack on certain membranes of the liver. Acetaldehyde is known to impede the mitochondrial electron transport system, which is responsible for oxidative metabolism and generation of ATP; as a result, the hydrogen ions that are generated in the mitochondria are shunted into lipid synthesis and ketogenesis. Binding of acetaldehyde to other molecules impairs the detoxification of free radicals and synthesis of proteins. Acetaldehyde also promotes collagen synthesis and fibrogenesis.

What changes take place in the liver resulting from the toxic effects of alcohol?

Fatty liver is characterized by the accumulation of fat in hepatocytes, a condition called steatosis. The liver becomes yellow, enlarges owing to excessive fat accumulation, and is characterized by inflammation and necrosis of liver cells. Alcoholic hepatitis is the intermediate stage between fatty changes and cirrhosis. It often is seen after an abrupt increase in alcohol intake and is common in "spree" drinkers. Alcoholic cirrhosis is the result of repeated bouts of drinking-related liver injury and designates the onset of end-stage alcoholic liver disease. The gross appearance of the early cirrhotic liver is one of fine, uniform nodules on its surface.

What is cirrhosis of the liver?

Cirrhosis is characterized by diffuse fibrosis and conversion of normal liver architecture into nodules containing proliferating hepatocytes encircled by fibrosis. The formation of nodules represents a balance between regenerative activity and constrictive scarring. The fibrous tissue that replaces normally functioning liver tissue forms constrictive bands that disrupt flow in the vascular channels and biliary duct systems of the liver. The disruption of vascular channels predisposes to portal hypertension and is complications; obstruction of biliary channels and exposure to the destructive effects of bile stasis; and loss of liver cells, leading to liver failure.

What are the factors that lead to the development of ascites?

An increase in capillary pressure due to portal hypertension and obstruction of venous flow through the liver, salt and water retention y the kidney, and decreased colloidal osmotic pressure due to impaired synthesis of albumin by the liver lead to the development of ascites. Diminished blood volume (i.e. underfill theory) and excessive blood volume (i.e. overfill theory) have been used to explain the increased salt and water retention by the kidney.

How does biliary venous obstruction lead to hemorrhoid formation?

With the gradual obstruction of venous blood flow in the liver, the pressure in the portal vein increases, and large collateral channels develop between the portal and systemic veins that supply the lower rectum. The dilation of the collaterals between the inferior and internal iliac veins may give rise to hemorrhoids.

A 16-year old female patient is brought to the clinic by her mother. She complains of recurrent fatigue and loss of appetite. Her mother states, "I am concerned because she has a yellow look in her eyes. It sort of comes and goes." While taking the client's history, the nurse finds that the client became sexually active 1 year ago and has had multiple partners during the past 12 months. On physical examination the physician notes an enlarged liver. The presumptive diagnosis is hepatitis C. What confirmatory test would the nurse expect to be ordered?

Serum aminotransferase, liver biopsy, complete blood count, and complete metabolic panel.

A 16-year old female patient is brought to the clinic by her mother. She complains of recurrent fatigue and loss of appetite. Her mother states, "I am concerned because she has a yellow look in her eyes. It sort of comes and goes." While taking the client's history, the nurse finds that the client became sexually active 1 year ago and has had multiple partners during the past 12 months. On physical examination the physician notes an enlarged liver. The presumptive diagnosis is hepatitis C. The client's test come back positive for hepatitis C. What medications might be ordered for this client?

Interferons, nucleotide and nucleotide analog antiretroviral agents, and pegylated interferon alfa-2a.

The liver has many jobs. One of the most important functions of the liver is to cleanse the portal blood of old and defective blood cells, bacteria in the bloodstream, and any foreign material. Which cells in the liver are capable of removing bacteria and foreign material from the portal blood?

Kupffer cells. Kupffer cells are reticuloendothelial cells that are capable of removing and phagocytizing old and defective blood cells, bacteria, and other foreign material from the portal blood as it flows through the sinusoid. Langerhans cells are stellate dendritic cells found mostly in the stratum spinosum of the epidermis. Davidoff cells are large granular epithelial cells found in intestinal glands.

Cholestasis is a condition in which there is a decrease in bile flow through the intrahepatic canaliculi and a reduction in secretion of water, bilirubin, and bile acids by the hepatocytes. Cholestasis can have more than one cause, but, in all types of cholestasis, there is what?

Accumulation of bile pigment in the liver. The morphologic features of cholestasis depend on the underlying cause. Common to all types of obstructive and hepatocellular cholestasis is the accumulation of bile pigment in the liver.

What is considered the normal amount of serum bilirubin found in the blood?

Usually, only a small amount of bilirubin is found in the blood; the normal level of total serum bilirubin is 0.1 to 1.2 mg/dL.

Many drugs are metabolized and detoxified in the liver. Most drug metabolizing occurs in the central zones of the liver. What condition is caused by these drug-metabolizing actions?

Centrilobular necrosis. Because of the greater activity of the drug-metabolizing enzymes in the central zones of the liver, these agents typically cause centrilobular necrosis.

Primary biliary cirrhosis is an autoimmune disease that destroys the small intrahepatic bile ducts causing cholestasis. It is insidious in onset and is a progressive disease. What are the earliest symptoms of the disease?

Unexplained pruritus. The earliest symptoms are unexplained pruritus or itching, weight loss, and fatigue, followed by dark urine and pale stools.

One of the jobs the liver performs is to export triglyceride. When the liver's capacity to export triglyceride is maximized, excess fatty acids accumulate in the liver. What is the disease these excess fatty acids contribute to?

Nonalcoholic fatty liver disease. When the capacity of the liver to export triglyceride is saturated, excess fatty acids contribute to the formation of fatty liver.

Ascites is an accumulation of fluid in the peritoneal cavity and usually occurs in advanced cirrhosis. What is the treatment of choice for ascites?

Diuretics. Because of the many limitations to sodium restriction, the use of diuretics has become the mainstay for treatment for ascites. A paracentesis may be done if diuretics do not correct the problem. A thoracentesis would never be done for ascites. DDAVP is given to decrease urine output, not to increase it.

A client is suspected of having liver cancer. What diagnostic tests would be ordered to confirm the diagnosis?

MRI of liver. Diagnostic methods include ultrasound, CT scans, and MRI. Liver biopsy may be used to confirm the diagnosis. The serum alpha-fetoprotein can be indicative of liver cancer but it is not confirmatory. An ultrasound of the liver is not confirmatory for liver cancer.

Gall stones are made up mostly of cholesterol. What is thought to be a precursor of gallstones?

Gallbladder sludge (thickened gallbladder mucoprotein with tiny trapped cholesterol crystals) is thought to be a precursor of gallstones.

What laboratory markers are most commonly used to diagnosis acute pancreatitis?

Lipase and amylase. Serum amylase and lipase are the laboratory markers most commonly used to establish a diagnosis of acute pancreatitis. Cholesterol and triglycerides are not used as laboratory markers for acute pancreatitis.

All diseases have risk factors. What is the most significant environmental risk factor for pancreatic cancer?

In pancreatic cancer, the most significant and reproducible environmental risk factor is cigarette smoking.

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